This application requests funds to purchase a precision X-Irradiator/ConeBeam CT for animal and cellular use at the University of Pennsylvania. This instrument (named Small Animal Radiation Research Platform-SARRP) represents a significant advance over any current instrument and was developed by Dr. John Wong at Johns Hopkins University, with support from the NCI through the Bioengineering Research Partnership mechanism. The SARRP addresses a critical need in Radiation Research for Image Guided Radiotherapy in rats and mice with resolution and accuracy comparable (on a scale- proportional basis) to therapy in humans. All former instruments for animal use have been derived from standard irradiators used for humans, large animals or industry. These represent, with minor improvements, 50-yr old technology. Until the development of this new machine (being commercially developed and sold by Gulmay Medical, Inc.) beam collimation for animal irradiators has been limited to shielding blocks and most irradiators had no freedom of movement for beam direction. The current instrument has the capability of 0.5 mm2 beam (a 400-fold improvement) and beam direction can be varied over 1200, with precise laser- based control of isocenter. The irradiation stage has 4-dimensional movement control (X-Y-Z and rotation) allowing complete flexibility of dose administration. Most importantly, the instrument is designed to be operated under low power as a cone- beam CT (CBCT) instrument and software for the instrument is modeled after human dose- planning, using the CBCT data. The instruments software control will also allow image fusion with other modalities, importantly PET and MRI. The instrument will be used in conjunction with other state-of-the art imaging equipment and will be initially installed in space occupied by the Radiation Research Division in the John Morgan Building and later moved to the new Perelman Center for Advanced Medicine at the University of Pennsylvania. Thus, in addition to providing advanced research capabilities for the Radiation Oncology Department, this instrument will open a world of opportunity for combined research with all other users of the Small Animal Imaging facilities at PENN. Importantly, numerous aspects of normal tissue research will become possible due to the precision of this device. Examples include realistic comparisons, using X-rays, of the scanned beam system designed for the Roberts Proton Radiotherapy center and selective irradiation of specific regions of mouse lung and brain. PUBLIC HEALTH RELEVANCE: This application requests support to purchase a unique animal irradiator, named the 'Small Animal Radiation Research Platform'(SARRP - Gulmay Medical). This instrument represents a unique, revolutionary, technical achievement that for the first time allows state-of-the art radiotherapy to be delivered to small animals (mice and rats) to closely recapitulate the parameters used for treatment of human cancer patients with radiotherapy. This will allow researchers in different fields (Radiation Oncology, Radiology, Pulmonary Medicine, etc), to study the effects of radiation on the tumor and surrounding normal tissues. This research will lead to better approaches to deliver radiation to the target, mitigate normal tissue toxicity and image changes in normal tissues before they manifest pathologically, thereby improving overall human health and quality of life.